Devices and Methods for the Treatment of Body Surface Disorders

This application claims the benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 62/520,504, filed Jun. 15, 2017, and entitled “Devices and Methods for the Treatment of Cutaneous Disorders.” and claims the benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 62/615,429, filed Jan. 9, 2018, und entitled “Devices and Methods for the Treatment of Cutaneous Disorders.” which are each incorporated herein by reference in their entireties.

The body surfaces of the body can be affected by various disorders. For example, many cutaneous disorders produce lesions on the skin. Some of these lesions take the form of epidermal growths on the skin. For instance, warts are small epidermal skin growths caused by viral infections, often found on the hands or feet. The most common type of wart is called Verruca vulgaris, which can be caused by multiple different strains of the human papilloma virus (HPV). On most parts of the body these warts may be referred to as common warts; on the feet, however, they may be referred to as plantar warts; when on the genitals they may be referred to as genital warts or condoloma. Other epidermal viral conditions such as Molluscum contagiosum resemble warts but are caused by distinct viruses. These viral mediated skin growths may be unsightly and may pose a significant risk for cancerous transformation and for spreading, making their removal desirable. Other superficial hyper-proliferative disorders resemble warts but are caused by non-viral mechanisms and include seborrheic keratosis, actinic keratosis, and porokeratosis.

Multiple modalities have been used to remove warts, Molluscum contagiosum, and other cutaneous diseases, including cryotherapy; surgical curettage; laser treatment; irritants such as salicylic acid and zinc oxide; acids such as nitric acid and squaric acid, immunotherapeutics such as imiquimod, 2,4-dinitrochlorobenzene and Candida antigen, and chemotherapeutics such as bleomycin, podophyllotoxin and 5-fluorouracil. Many of the therapies can be painful, while others can leave disfiguring scars and/or require daily application. Perhaps most troubling, however, is that many of these cutaneous disorders remain recalcitrant even after multiple follow-up treatments. Accordingly, improved therapies are needed for treating these conditions.

Described herein is an applicator device for dispensing a composition for topical administration of the composition to a subject. In some embodiments, the composition may be a pharmaceutical composition. In come embodiments, the applicator device may be used to topically administer a composition to a subject. The applicator device may topically administer the composition to various body surfaces, including, but not limited to, skin, mucous membranes, exposed soft tissue or internal organs, genitalia, penis, vagina, anus, nails, hair, nose, eye, ear, or mouth, including lips, teeth, longue, and gums. These body surfaces may be intact, abraded or wounded or exposed due to injury or surgical exposure.

Devices, methods, kits, and systems of treating one or more conditions, such as a body surface condition, are described herein. A body surface condition is a condition affecting a portion of the body that can be treated via topical administration of a composition onto the body. According to one aspect, an applicator device is used to dispense a composition onto an area of the body affected by a condition. The applicator device may be constructed and arranged to deliver a controllable amount of the composition to a specific location of the body without getting the composition on other areas of the body.

According to one aspect, the applicator device is able to produce droplets that can be dispensed onto a body surface without making physical contact between the applicator device and the body surface. As a result, when administering the composition, the user can avoid contacting the body surface with the applicator device (e.g., to avoid physically disturbing the body surface and/or to avoid contaminating the dispenser tip or the pharmaceutical composition) and holds the dispenser tip at a small distance from the desired treatment site when administering the pharmaceutical composition, allowing the pharmaceutical composition to be dispensed onto the body surface. This is in contrast to an applicator device having a brush applicator (foam, cloth, or fuzzy) or roll-on head that must contact body surface in order to administer the composition. Another aspect of this dispenser tip is that it may minimize the surface area and time of exposure of the solution to the air, reducing the amount, of solvent loss and thereby maintaining the concentration of the solution that is applied to the body surface compared to other applicator tips.

Another aspect of the present disclosure provides an applicator device for dispensing a pharmaceutical composition to topically treat a condition. The applicator device may comprise; a tube, an ampule positioned within the tube, a pharmaceutical composition contained within the ampule, a dispenser tip attached to the tube, the dispenser tip having a tapered tip, and a filter positioned within the tapered tip of the dispenser tip. The filter may be constructed and arranged to permit passage of fluid and inhibit passage or broken ampule shards having a particle size of at least 150 μm.

Another aspect of the present disclosure provides an applicator device for dispensing a pharmaceutical composition to topically treat a condition. The applicator device ray comprise: a tube, a pharmaceutical composition contained within the tube, a dispenser tip coupled to the tube, and a cap having an opening for receiving the dispenser tip. The cap may have a closed position in which at least a portion of the dispenser tip is passed through the opening. The cap may be coupled to the dispenser tip and positioned over at least a portion of the dispenser tip. When the cap is in the closed position, venting of the dispenser tip is permitted through the opening of the cap. In some embodiments, the applicator device includes an ampule, and the pharmaceutical composition is contained within the ampule.

Another aspect of the present disclosure provides a method of topical administration of a pharmaceutical composition to a subject. The method may comprise: squeezing the tube of an applicator device to break an ampule within the tube to release a pharmaceutical composition contained within the ampule while the cap is in a closed position covering at least a portion of a dispenser tip of the applicator device, moving the dispenser tip toward a subject, and dispensing the pharmaceutical composition from the dispenser tip onto the subject.

Another aspect of the present disclosure provides a kit for dispensing a pharmaceutical composition for topically treating a condition. The kit may include a plurality of applicator devices. Each applicator device may comprise: a tube, an ampule positioned within the tube, a pharmaceutical composition contained within the ampule, a dispenser tip attached to the tube, the dispenser tip having a tapered tip, and a filter positioned within the tapered tip of the dispenser tip, the filter being constructed and arranged to permit passage of fluid and inhibit passage of broken ampule shards having a particle size of at least 150 μm. The kit may also include instructions for use. In some embodiments, the kit may include external packaging to protect the applicator and/or drug from light or moisture, aids for opening the applicator and/or promotional materials. The pharmaceutical composition may comprise cantharidin, acetone, ethanol, a plasticizer, and a film-forming agent.

Another aspect of the present disclosure provides methods of treating a subject having an affected body surface area, such as, but not limited to, skin, eye, ear, mouth, nose, vagina, or anus. The method can comprise squeezing the tube of an applicator device to break an ampule within the tube to release a pharmaceutical composition contained within the ampule while the cap is in a closed position covering at least a portion of a dispenser tip of the applicator device. The method can also comprise moving the dispenser tip toward an affected body surface area of a subject and dispensing the pharmaceutical composition from the dispenser tip onto the affected body surface area.

According to one aspect, patients may receive one treatment every 3 weeks, plus or minus 4 days (i.e. one treatment every 17 to 25 days); a first treatment at week 0, a second treatment at week 3, a third treatment at week 6, and a fourth treatment at week 9.

One aspect of the present disclosure provides a method of treating a dermatological condition. The method can comprise applying a pharmaceutical composition to a subject, which may include: squeezing a tube of an applicator device to break an ampule within the tube to release a pharmaceutical composition contained within the ampule and dispensing the pharmaceutical composition from the dispenser tip onto a plurality of skin lesions on a subject. The method can include performing the step of applying the pharmaceutical composition four tines, once every 17 to 25 days, where the pharmaceutical composition comprises cantharidin, acetone, ethanol, a plasticizer, and a film-forming agent.

Another aspect of the present disclosure provides a method of treating a dermatological condition. The method may include treating a plurality of skin lesions on a subject by dispensing a pharmaceutical composition out of an applicator device onto the skin lesions, where the pharmaceutical composition comprises cantharidin and one or more excipients, and where treating the skin lesions with the applicator device clears more of the skin lesions than treating of the skin lesion with a stick applicator in the same amount of time.

Another aspect of the present disclosure provides a method of treating a dermatological condition. The method may include treating a plurality of skin lesions on a subject by dispensing a pharmaceutical composition out of an applicator device onto the skin lesion. The pharmaceutical composition may comprise cantharidin and one or more excipients. Treating the skin lesions with the applicator device may clear more of the skin lesions than treating of the skin lesion with a stick applicator in the same amount of time.

Another aspect of the present disclosure provides an applicator device for dispensing a pharmaceutical composition for topical administration of the pharmaceutical composition to a subject. The device may include a tube, a pharmaceutical composition contained within the tube, and a dispenser tip attached to the tube. The dispenser tip may have a tapered tip that ends in a distal opening having an internal diameter of less tian about 0.013 inches and external diameter of less than about 0.034 inches.

Another aspect of the present disclosure provides a method of treating a dermatological condition. The method may include applying a pharmaceutical composition to a subject, which may include squeezing a tube of an applicator device. The applicator device may have a dispenser tip having a tapered tip that in a distal opening having an internal diameter of less than about 0.013 inches and external diameter of less than about 0.034 inches. The method may also include dispensing the pharmaceutical composition from the dispenser tip onto a plurality of skin lesions on a subject.

Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying figures, in cases where the present specification and a document incorporated by reference include conflicting and/or inconsistent disclosure, the present specification shall control.

In one set of embodiments, an applicator device used to dispense a composition is provided. The applicator device may be used to topically administer the composition to a body surface of a subjectdepicts an illustrative embodiment of an applicator devicehaving a tubeand a cap.depicts an exploded view of the applicator device. In some embodiments, the applicator deviceincludes a reservoir(e.g., an ampule) for holding a pharmaceutical composition. In some embodiments, the applicator deviceincludes a dispenser tipand a filter.depicts a side view of the applicator device, andis a cross-sectional view of the applicator device oftaken along line-of. In some embodiments, the applicator device may be used to deliver any suitable composition for topical administration of the composition to a body surface.

The relative position of each of the components of the applicator deviceaccording to some embodiments can be seen in. In some embodiments, the ampuleis positioned within the tube. In some embodiments, the filteris positioned within the dispenser tip. In some embodiments, the caphas a closed position in which the capcovers the distal opening of the dispenser tip. In some embodiments, in the closed position, the cap is removably coupled to the dispenser tip.

In some embodiments, the pharmaceutical composition is stored within the ampule. The ampulemay be constricted and arranged to be a sealed vessel to prevent exposure of the pharmaceutical composition, in particular the active ingredient, to ambient air, which may aid in preserving the stability of the pharmaceutical composition and/or active ingredient. In some embodiments, the ampule is made of glass. In some embodiments, the ampule is made of plastic.

According to some embodiments, in use, a user may initiate release of pharmaceutical composition by squeezing the tube, which causes the ampuleto break, resulting in release of pharmaceutical composition from inside the ampule, in some embodiment, a user squeezes the tube to break the ampule by squeezing a paperboard or cardboard sleeve or other ampule crushing device around the tube. With the composition released from the ampule, the pharmaceutical composition may flow from the broken ampule toward the dispenser tip. In some embodiments, squeezing of the tube may cause the composition to flow out of the dispenser tip. The filtermay be constructed and arranged to permit passage of the pharmaceutical composition, while inhibiting passage of shards from the broken ampule.

In some embodiments, a user may keep the cupin the closed position when initiating release of the pharmaceutical composition (e.g., when squeezing the tubeto break the ampule). In some embodiments, keeping the capon while the ampule is being broken may help to avoid premature dispensing of the pharmaceutical composition out of the dispenser tip. In other embodiments, however, a user may initiate release of the pharmaceutical composition with the capoff. In some embodiments, the unit can be facing up, down or at an angle when the ampule is broken.

In some embodiments, when the user (e.g., healthcare professional) is ready to administer the pharmaceutical composition to a subject, the user removes the cap, exposing the distal opening of the dispenser tip. The user then moves the dispenser tiptoward the desired treatment sites on the body surface of the subject. In some embodiments, the dispenser tip is constructed and arranged such that the user must exert a threshold amount of force on the tube (e.g., squeeze the tube) to create a sufficient amount of pressure inside the tube to cause an amount of the pharmaceutical composition to be released out of the dispenser tip. In some embodiments, air may be expelled prior to the pharmaceutical composition resulting in the creation of an internal vacuum. In some embodiments, gravity alone is sufficient to cause the pharmaceutical composition to flow out of the dispenser tip and onto the body surface of the subject.

In some embodiments, cessation of the applied force on the tube (e.g., user stops squeezing the tube), may cause the pharmaceutical composition to be drawn back into the dispenser tip. In some embodiments, this movement of the pharmaceutical composition back into the dispenser tip may be caused by creation of vacuum inside the tubethat occurs due to expansion of the internal volume of the tubefrom a first volume when in a squeezed state to a larger volume when the squeezing ceases, and the tube is permitted to revert back to it's original unstressed shape. In some embodiments, this movement of the pharmaceutical composition back into the dispenser tip may be caused or facilitated by the geometry of dispenser tip, which will be discussed in a later section.

In some embodiments, the applicator device is able to produce droplets that can be dispensed onto the body surface without making physical contact between the applicator device and the body surface.

In other embodiments, however, the user may contact the body surface with the distal end of the dispenser tip during administration of the pharmaceutical composition.

In some embodiments, a user dispenses an amount of the pharmaceutical composition from the applicator device onto an intermediate applicator, such as a cotton swab stick applicator, a, stick, a toothpick, a capillary tube, a cotton ball, or any other suitable applicator, which is then used to apply the pharmaceutical composition to a treatment site.

In some embodiments, the applicator device may have a dispenser tip. In some embodiments, the dispenser tip is a separate component from the tube. In some embodiments, the dispenser tip is integrally formed with the tube, such that the dispenser tip and tube form one monolithic component. In some embodiments, the dispenser tip includes a tapered tip through which a pharmaceutical composition flows, the dispenser tip may have a digital opening through which the pharmaceutical composition exits the applicator device.

One illustrative embodiment of a dispenser tip is shown in. The dispenser tipmay include a tapered tip, which may include an opening, in some embodiments, the openingis at the distal end of the tapered tip.

provide dimensions (shown in inches for distances and degrees for angles) for one illustrative embodiment of a dispenser tip. It should be understood that such dimensions are provided as an illustrative example, and that the applicator device may include a dispenser tip having different dimensions than those shown in.

In some embodiments, the openinghas an outer diameter of about 0.01 inches to about 0.1 inch, about 0.015 inches to about 0.9 inches, about 0.0175 inches to about 005 inches, about 0.02 inches to about 0.04 inches, about 0.025 inches to about 0.035 inches, about 0.028 inches to about 0.032 inches, or about 0.032 inches. In some embodiments, the openinghas an inner diameter of about 0.001 inches to about 0.1 inches, about 0.005 to about 0.05 inches, about 0.0075 to about 0.05 inches, about 0.01 inches to about 0.03 inches, or about 0.012 inches.

According to one aspect of the invention, in some embodiments, the dispenser tip includes a tapered tip, which may have an outer surface and an inner surface. The pharmaceutical composition from the applicator device flows through and may contact the inner surface of the dispenser tip. The inner and/or outer surfaces may be tapered (i.e. decrease in size), in the direction moving from a proximal end to a distal end of the dispenser tip. In some embodiments, the angle of the taper of the outer surface may be different than the angle of the taper of the inner surface. In some embodiments, the taper angle of the outer surface changes across the length of the tapered tip. In some embodiments, the taper angle of the inner surface changes across the length of the tapered tip. In some embodiments, a first portion of the outer surface of the tapered tip may have a first taper angle, and a second portion of the outer surface may have a second, different taper angle. In some embodiments, a first portion of the inner surface of the tapered tip may have a first taper angle, and a second portion of the inner surface may have a second, different taper angle. In some embodiments, the second taper angle is smaller than the first taper angle. In some embodiments, the inner and/or the outer surfaces may have a portion that is tapered and a portion that is not tapered.

In one illustrative embodiment, shown in, which depicts a detail view of the encircled regionof the dispenser tip of, the tapered tiphas an outer surfaceand an inner surface. The inner surfacehas a first portionthat is tapered, and a second portionthat is straight, or has a taper angle that is different than that of the first portion. In some embodiments, the second portion may have a taper angle that is smaller than that of the first portion. As also seen in the embodiment of, the taper angle of the outer surfaceis different than that of the taper angle of the first portionof the inner surface.

In some embodiments, the inner surface of the dispenser tip has a taper angle of about 1 to about 5 degrees, about 2 to about 4 degrees, about 2.5 to about 3.5 degrees, about 2.5 to about 4 degrees, about 2.5 to about 4.5 degrees, about 2.5 to about, 5 degrees, about 2.5 to about 5.5 degrees, or about 3.00 degrees.

In some embodiments, the outer surface of the dispenser tip has a taper angle of about 1 to about 10 degrees, about 2 to about 9 degrees, about 2.5 to about 5.5 degrees, about 2.5 to about 7 degrees, about 3 to about 8 degrees, about 4 to about 7 degrees, about 4.5 to about 5.5 degrees, about 4.7 degrees to about 5 degrees, or about 4.80 degrees.

The tapered tip may have a longitudinal axis L, as shown in. The tapered tip may be rotationally symmetric about the longitudinal axis L.

The tapered tip may have a length along longitudinal axis L of about 0.1 to about 2 inches, about 0.3 to about 1.7 inches, about 0.5 inches to about 1.5 inches, about 0.7 inches to about 1.4 inches, about 0.8 inches to about 1.3 inches, about 0.9 inches to about 1.3 inches, about 1.1 to about 1.3 inches, or about 1.1 inches to about 1.2 inches.

In some embodiments, the inner surface of the dispenser tip at a distal portion of the tip has a decreased taper as compared to the rest of the inner surface, or is a straight-walled channel with no taper. In some embodiments, the distal portion of the tip having a straight-walled inner channel spans a distance along the longitudinal axis L of the dispenser tip that is about 0.01 to about 0.1 inch long, about 0.01 to about 0.05 inches long, about 0.02 to about 0.04 inches long, about 0.025 to about 0.035 inches long, or about 0.029 inches long.

According to one aspect of the invention, the site and shape of the tapered tip may help to control dispense of droplets of the composition onto desired areas of skin. In some embodiments, the tapered tip produces droplets of the composition having a size of about 0.1 mm to about 10 mm, about 0.5 mm to about 9 mm, about 0.7 mm to about 6 mm, or about 1 mm to about 4 mm in size. The controlled size of the droplet produced by the applicator tip may help to keep dispensed composition within a small area of skin and avoid dispensing of composition on unwanted areas of skin. e.g., limiting treatment only to areas of skin that are affected by a skin condition.

In some embodiments, the volume of each droplet of the composition administered by the applicator device may be at least 1 uL, at least 2 uL, at least 3 uL, at least 4 uL, at least 5 uL at least 6 uL, at least 7 uL, at least 8 uL at least 9 uL, at least 1.0 uL at least 15 uL at least 20 uL at least 30 uL, at least 50 uL, at least 100 uL, at least 200 uL at least 300 uL, at least 500 uL, at least 80 uL, at least 900 uL at least 1 mL or at least 5 mL. In some embodiments, the volume of each droplet administered by the applicator device may be less than 5 mL, less than 1 mL, less than 900 uL, less than 800 uL, less than 700 uL, less than 600 uL, less than 500 uL less than 400 uL, less than 300 uL, less than 200 uL, less than 100 uL, less than 90 uL less than 80 uL, less than 70 uL, less than 60 uL, less than 50 uL, less than 45 uL, less than 40 uL, less than 35 uL, less than 30 uL, less than 25 uL, less than 20 uL, less than 15 uL, less than 12 uL less than 10 uL, less than 9 uL, less than 8 uL, less than 7 uL less than 6 uL or less than uL. All combinations of the above-referenced ranges are possible. For example, the volume of each droplet administered by the applicator device may be about 1 uL to about 5 m, or about 2 uL, to about 1 mL or about 3 uL, to about 900 uL, or about 4 uL to about 900 uL, or about 5 uL to about 500 uL, or about 5 uL, to about 400 uL or about 5 uL, to about 200 uL, or about 5 uL to about. 100 uL, or about 5 uL, to about 50 uL, or about 5 uL to about 20 uL, or about 5 uL to about 10 uL.

The dispenser tip may be able to deliver a plurality of droplets. e.g., 5, 10, 20, 30, 40, 50, 60 or more droplets.

In some embodiments, the applicator device includes a drip guard to aid in preventing the pharmaceutical composition from sliding down the sides of the device onto a user's hand that is holding the device. In some embodiments, the drip guard may be in the form of a moat having a trough for catching the pharmaceutical composition. In some embodiments, the drip guard surrounds at least a portion of the tapered tip of the dispenser tip.

As seen in, the dispenser tipincludes a drip guardin the form of an annular ring forming an annular troughfor receiving one or more droplet flowing down the sides of the tapered tip. The trough may be sized to hold at least 1, at least 2, at least 3, at least 4 or at least 5 droplets, or any other suitable number of droplets.

As seen in, the dispenser drip guardsurrounds a proximal portion of the tapered tip.

In some embodiments, the drip guard defines the largest outer diameter of the dispenser tip. For example as seen in, the diameter of the drip guardis the largest diameter of the dispenser tip.

In some embodiments, the drip guard has a diameter of about 0.1 to about 1 inch, about 0.15 to about 0, inches, about 0.2 to about 0.6 inches, about 0.3 to about 0.5 inches, about 0.3 to about 0.45 inches, or about 044 inches.

In some embodiments, the applicator device enables the ability to routinely deliver material with the sane concentration as the concentration in the ampule and that at the time of contact with the skin the material delivered has a concentration of or about 0.7% w/v.

In some embodiments, the dispenser tipincludes an attachment portionthat may interface with the tube. In some embodiments, the attachment portionis attached to the tube. For example, as shown in, at least a portion of the attachment portionmay contact at least a portion of the tube. The dispenser tipand tubemay be attached to one another via adhesive, welding, ultrasonic welding, UV glue, interference fit, mechanical interlock, threaded engagement, snap fit engagement, fasteners, or via any other suitable arrangement. One or more intermediate components may be used to attach the dispenser tip to the tube. In some embodiments, the dispenser tipand tubearm attached to one another to form a hermetic seal.

The tip may be made of a polymeric material, such as plastic or thermoplastic. In some embodiments, the tip is made of a polypropylene homopolymer. In some embodiments, the tip is made of a transparent or translucent material. The transparent or translucent material may permit a user to see composition flowing through the tip during administration. In some embodiments, the composition is colored to help the user see the composition as it flows through the tip. Other portions of the applicator device may also be transparent or translucent, such as the tube, the ampule, and the cap.